“Given that neither drug has ever been approved for weight loss independently, and the FDA is clueless about how any of the drugs work in the brain independently, or in combination, as treatment for weight reduction, this should signal serious concern.”

By Kelly Patricia O’Meara
Published by CCHR International
The Mental Health Industry Watchdog
January 30, 2017

Like so many of today’s pharmaceutical chemical behavioral fixes, one of the newest weight loss medication for obesity to hit the market, Contrave, misleadingly inspires hope that a mind-altering pill will help shed unwanted pounds but, in reality, the hype outweighs the hope. Questions are being raised about the serious, and possibly deadly, adverse reactions associated with this cocktail drug.[1]

Contrave, made by Orexigen Therapeutics, is not a “new” drug as implied, but, rather, is actually the result of repackaging two older drugs: the antidepressant bupropion (Wellbutrin for depression) (Zyban for smoking cessation) and the alcohol/addiction-treatment drug, naltrexone (ReVia/Vivitrol),[2] neither of which is individually approved for weight loss but, not surprisingly, come with their own lengthy list of adverse reactions.

In the case of bupropion, adverse reactions include: abnormal dreams, agitation, anxiety, confusion, delusions, depression, hallucinations, hostility, tachycardia and cardiac arrhythmias and mania/hypomania to name a few.[3] And, in the case of naltrexone, possible adverse effects include depression and suicidal ideation or attempts.[4] The Food and Drug Administration (FDA) warned the manufacturer of the naltrexone product, Vivitrol, that “Patients should be warned of the risk of hepatic [liver] injury” and to seek medical attention if they experience “symptoms of acute hepatitis.”[5]

More importantly, because Contrave includes the psychiatric mind-altering drug bupropion, it must carry the FDA’s most serious “Black-box” warning for causing suicidality.[6]

While Contrave purports to help in shedding unwanted weight, the outcomes as reported during clinical trials are less than miraculous. According to Consumer Reports, “not everyone who takes Contrave will experience meaningful weight loss: In one trial, about 42 percent of people who took Contrave lost 5 percent or more of their weight compared to 17 percent of those who took a placebo.”[7]

A review of the clinical trial data by the Consumer Reports Best Buy Drugs program determined that, “One of the largest clinical trials to date of Contrave shows obese and overweight people who took the drug for up to 56 weeks lost an average of 12 pounds (or about 5 percent of their body weight), compared with an average of 3 pounds (or one percent of their body weight) among those who took a placebo. Both groups were also put on a reduced calorie diet, exercised, and received behavioral counseling.”

Putting that data into perspective, Consumer Reports explained, “We estimated that a person weighing 220 pounds who takes Contrave for a year could expect to lose about 12 pounds total: 9 pounds from the drug itself and 3 pounds from diet and exercise.”

Because questions have been raised about Contrave causing cardiovascular problems, the FDA has required Orexigen to conduct further clinical trials to determine whether the drug is safe for the heart. Orexigen had begun and stopped two heart trials prior to completion, and the FDA is allowing the pharmaceutical company until 2021 to provide its heart trial results.[8]

Keeping a potentially dangerous drug on the market is not new for the FDA. A spokesman for the FDA explained to Consumer Reports that “It was premature to draw any conclusions from Contrave’s first heart trial, so determining whether Contrave poses a risk to the heart will require completing the new study.” In essence, the public is the guinea pig and will act as a defacto clinical trial over the next five years, when Orexigen’s heart study is expected to be completed.

Given the concerns surrounding the possibility of heart problems associated with Contrave, one cannot help but recall the number of deaths and harm associated with another popular weight loss drug, Fenfluramine/phentermine or Fen-Phen. Due to increasing numbers of women who took Fen-Phen experiencing valvular heart disease and pulmonary hypertension, the FDA withdrew the drug from the market in 1997.[9] Psychiatrists have tested fenfluramine, the offending half of the prescription diet drug, for “seasonal affective disorder” (SAD) and ADHD, despite its risks.

Beyond the known dangerous side effects associated with Contrave, it is important to note that, like all psychiatric drugs, the mode/mechanism of action—that is, how the drug actually works—is not known for either of the two drugs that make up Contrave.

In other words, according to the FDA, “The neurochemical mechanism of the antidepressant effect of bupropion [Wellbutrin/Zyban] is not known.”[10] As is the case of Naltrexone: “The neurobiological mechanisms responsible for the reduction in alcohol consumption observed in alcohol-dependent patients treated with naltrexone are not entirely understood.”[11]

Yet, despite having no scientific certainty about how either of these drugs works in the brain to treat the symptoms for which they have independently been approved, the FDA has approved the combination of drugs for weight loss, which the federal drug agency further reports, “The exact neurochemical effects of Contrave leading to weight loss are not fully understood.” [12]

Given that neither drug has ever been approved for weight loss independently, and the FDA is clueless about how any of the drugs work in the brain independently, or in combination, as treatment for weight reduction, this should signal serious concern. With almost 13 million of U.S. children ages 2 to 19 and 78 million adults considered obese, and with psychiatrists suggesting that obesity is a behavioral disorder, this is a lucrative market for both psychiatrists and Orexigen Therapeutics. That the FDA continues to approve mind-altering drugs to treat physical conditions is bad enough, but is compounded by the minimal results of Contrave and the serious adverse reactions of both drugs in combination.

References:

[1] “Is Contrave Worth Trying If You Want to Lose Weight?” Consumer Reports, 5 May 2016, http://consumerreports.org/drugs/is-contrave-worth-trying-to-lose-weight/.

[2] Ibid.

[3] “Wellbutrin Side Effects,” Drug.com, accessed 26 Jan 2017, https://www.drugs.com/sfx/wellbutrin-side-effects.html.

[4] “Naltrexone Side Effects,” Drug.com, accessed 26 Jan 2017, https://www.drugs.com/sfx/naltrexone-side-effects.html.

[5] Hubert, Susannah K., MPH. “NDA 021897, Vivitrol® (naltrexone for Extended-release Injectable Suspension).” Letter to Nancie A. Zecco, Senior Regulatory Associate. 04 Nov 2010, http://www.fda.gov/downloads/Drugs/…/UCM233866.pdf.

[6] “CONTRAVE (naltrexone HCl and bupropion HCl)” FDA.gov, accessed 26 Jan 2017, http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/200063s000lbl.pdf.

[7] Op cit., Consumer Reports.

[8] Ibid.

[9] “Cardiac Valvulopathy Associated with Exposure to Fenfluramine or Dexfenfluramine: U.S. Department of Health and Human Services Interim Public Health Recommendations, November 1997,” CDC, https://www.cdc.gov/mmwr/preview/mmwrhtml/00049815.htm; David Kohn, “Investigating Fen-Phen,” 60 Minutes, 9 Feb 1999, http://www.cbsnews.com/news/investigating-fen-phen/.

[10] Prescribing Information, WELLBUTRIN (bupropion hydrochloride), FDA.gov, April 2004, http://www.fda.gov/ohrms/dockets/ac/04/briefing/2004-4065b1-20-tab11A-Wellbutrin-Tabs-SLR028.pdf.

[11] VIVITROL (naltrexone for extended-release injectable suspension), FDA.gov, May 2009, http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/021897s005s010lbl.pdf.

[12] “CONTRAVE (naltrexone HCl and bupropion HCl),” FDA.gov, accessed 26 Jan 2017, http://www.accessdata.fda.gov/drugsatfda_docs/label/2014/200063s000lbl.pdf.